Hypoxia-inducible factor-1? promotes endometrial stromal cells migration and invasion by upregulating autophagy in endometriosis.
Ontology highlight
ABSTRACT: Endometriosis is a benign gynecological disease that shares some characteristics with malignancy like migration and invasion. It has been reported that both hypoxia-inducible factor-1? (HIF-1?) and autophagy were upregulated in ectopic endometrium of patients with ovarian endometriosis. However, the crosstalk between HIF-1? and autophagy in the pathogenesis of endometriosis remains to be clarified. Accordingly, we investigated whether autophagy was regulated by HIF-1?, as well as whether the effect of HIF-1? on cell migration and invasion is mediated through autophagy upregulation. Here, we found that ectopic endometrium from patients with endometriosis highly expressed HIF-1? and autophagy-related protein LC3. In cultured human endometrial stromal cells (HESCs), autophagy was induced by hypoxia in a time-dependent manner and autophagy activation was dependent on HIF-1?. In addition, migration and invasion ability of HESCs were enhanced by hypoxia treatment, whereas knockdown of HIF-1? attenuated this effect. Furthermore, inhibiting autophagy with specific inhibitors and Beclin1 siRNA attenuated hypoxia triggered migration and invasion of HESCs. Taken together, these results suggest that HIF-1? promotes HESCs invasion and metastasis by upregulating autophagy. Thus, autophagy may be involved in the pathogenesis of endometriosis and inhibition of autophagy might be a novel therapeutic approach to the treatment of endometriosis.
SUBMITTER: Liu H
PROVIDER: S-EPMC5489654 | biostudies-literature | 2017 Jun
REPOSITORIES: biostudies-literature
ACCESS DATA